Surveillance to track and characterize antimalarial resistance trends in Ugandan Plasmodium falciparum parasites (STARTUP)

监测追踪和表征乌干达恶性疟原虫寄生虫的抗疟药耐药性趋势（STARTUP）

• 批准号: 10567404
• 负责人: Melissa D Conrad
• 金额: $ 78.91万
• 依托单位: UNIVERSITY OF CALIFORNIA, SAN FRANCISCO
• 依托单位国家: 美国
• 财政年份: 2022
• 资助国家: 美国
• 起止时间: 2022-12-20 至 2027-11-30
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10567404
• 关键词: Address; Africa; Age; Anti-malarial drug resistance; Antimalarials; Artemisinins; Automobile Driving; Biological Assay; Blood; CRISPR/Cas technology; Cessation of life; Clinical; Collection; Combined Modality Therapy; Communication; Country; Detection; Drug Exposure; Drug resistance; Epidemiologic Factors; Epidemiology; Evolution; Fright; Genetic; Genetic Polymorphism; Genotype; Geography; Goals; Growth; Hot Spot; Household; Immunity; In Vitro; Incidence; Individual; Infection; Infrastructure; Intervention; Laboratories; Malaria; Maps; Mediating; Metadata; Modernization; Molecular; Molecular Epidemiology; Mutation; Parasite resistance; Parasites; Parasitology; Pharmaceutical Preparations; Phenotype; Plasmodium falciparum; Policies; Policy Maker; Population; Population Genetics; Positioning Attribute; Predisposition; Prevalence; Public Health; Reporting; Research Activity; Resistance; Resolution; Rwanda; Site; Testing; Time; Uganda; Urbanicity; Validation; candidate validation; deep sequencing; fitness; improved; molecular marker; novel; novel therapeutics; response; transmission process; trend

PROJECT SUMMARY/ABSTRACT: New studies in Uganda and Rwanda have reported increasing prevalence of mutations in pfkelch13 (K13) associated with delayed parasite clearance following clinical or in vitro treatment with artemisinins, suggesting that fears that resistance of Plasmodium falciparum to artemisinins will emerge in Africa, where >90% of malaria cases and deaths occur, have been realized. However, the extent of resistance to components of artemisinin-based combination therapies (ACTs) is not well understood. Our ongoing research activities and well-established infrastructure in Uganda put us in a unique position to rapidly address urgent needs for improved surveillance and characterization of resistance to artemisinins and partner drugs in Uganda. Benefitting from a network of 80 surveillance sites across the country and modern laboratories in Kampala and Tororo, we will use molecular, parasitological and epidemiological approaches a) to evaluate the origins, prevalence and distribution of known markers of artemisinin and ACT partner drug resistance and to characterize the genetic background(s) that facilitate the establishment and spread of resistance phenotypes, b) assess associations between genotypes and drug susceptibility/fitness phenotypes, and c) assess ecological and epidemiological factors that facilitate the evolution of resistance. With resistance to important drugs still geographically focal, our goal is to identify key drivers of its emergence and spread, and then to promptly inform public health leaders on the best means of blunting the spread of resistance across Africa.

项目摘要/摘要： 乌干达和卢旺达的新研究报道了PFKELCH13突变患病率的增加（K13） 与青蒿素治疗后，与临床或体外治疗后的延迟寄生虫清除相关，这表明 担心恶性疟原虫对青蒿素的抗性会在非洲出现，> 90％ 发生疟疾病例和死亡已经实现。但是，对组成部分的抵抗程度 基于青蒿素的组合疗法（ACT）尚不清楚。我们正在进行的研究活动以及 乌干达建立良好的基础设施使我们处于一个独特的立场，以快速满足紧急需求 改善了对乌干达青蒿素和伴侣药物抵抗的监视和表征。 从全国各地的80个监视站点以及坎帕拉的现代实验室和现代实验室中受益 Tororo，我们将使用分子，寄生学和流行病学方法a）评估起源， 青蒿素的已知标记和ACT伴侣耐药性的患病率和分布和分布 表征有助于建立和传播抗性表型的遗传背景， b）评估基因型与药物敏感性/适应性表型之间的关联，c）评估 促进抗性进化的生态和流行病学因素。抵抗重要 在地理位置上，药物仍然是焦点，我们的目标是确定其出现和传播的关键动力，然后识别 迅速向公共卫生领导人告知削弱抵抗运动在非洲的最佳手段。